Lung cancer is the leading cause of cancer related mortality for both men and women, with an anticipated 174,470 new cases and 162,460 deaths in 2006. Besides quitting or preventing smoking, means to reduce mortality from lung cancer are limited. Recent studies suggested that vitamin D may reduce incidence and diminish progression across a spectrum of cancers including lung cancer. Our preliminary results suggested that the joint effects of surgery season and vitamin D intake are associated with recurrence free survival and overall survival in early stage non-small cell lung cancer (NSCLC) patients. This project will investigate comprehensively the roles of vitamin D in important clinical outcomes of all stages of NSCLC patients. In a large prospectively-collected cohort of NSCLC patients, we will investigate whether higher serum levels of vitamin D (25-hydroxyvitamin D, the primary circulating form of vitamin D) at the time of lung cancer diagnosis/treatment initiation are associated with better prognosis in both early and advanced stage NSCLC patients. We will then investigate the role of polymorphic vitamin D receptor (VDR) and CYP24 genes in altering NSCLC prognosis. Finally, we will study the role of VDR and CYP24 polymorphisms in modifying the association between vitamin D and the NSCLC prognosis. Serum vitamin D levels are measured using radioimmunosorbant assay, dietary and supplement vitamin D intake are obtained using food frequency questionnaires, while candidate polymorphisms are evaluated using PCR-based genotyping techniques. The methods of Kaplan-Meier (logrank tests) and Cox proportional hazards models (adjusting for important covariates) will be used for outcomes analysis. The outcomes of interest for potentially curable early NSCLCs (stage I-IIIA) are recurrence-free survival and overall survival. For advanced NSCLCs (stage IIIB- IV), the outcomes are progression free survival and overall survival. We hope that in accomplishing this project, we will have a better idea of how vitamin D levels at the time of diagnosis/treatment initiation may affect how well a patient does after the diagnosis of lung cancer and how vitamin D may alter the effects of lung cancer treatment. The ultimate goal of this research is to individualize therapies for every patient. [unreadable] [unreadable] [unreadable]